Fig. 1

Histopathology findings of FCD ILAE Type IIa and IIb. A 42-year-old male individual with frontal lobe epilepsy since age 5 years (ID3). The MRI was suspicious for a bottom-of-sulcus FCD with transmantel sign. Histopathology confirmed, however, FCDIIa and a pathogenic DEPDC5 mosaicism. The arrow points to the sharp border between the cortical FCDIIa and the normal-appearing white matter (WM). NCx—adjacent normal 6-layered neocortex. Neurofilament SMI32 immunohistochemistry. Scale bar = 2.5mm (applies also to B). Higher magnification in C reveals dysmorphic neurons with a predominant vacuolizing phenotype (red arrow) suggesting accumulation of lipofuscins and an altered autophagy pathway. Scale bar = 100 µm (applies also to D). Same neurons were also labeled with antibodies directed against the phospho-S6-Ser236 epitope (E). The black arrow in (E) points to a neuron with a vacuolizing phenotype. Scale bar in E = 100 µm, applies also to (F); B 19-year-old male individual with frontal lobe epilepsy since age nine years (ID15), histopathological confirmed FCDIIb at a bottom-of-sulcus (BoS; higher magnification in D) and a pathogenic MTOR mosaicism. Dysmorphic neurons and balloon cells were aggregated in the neocortex and white matter (arrow in B) compatible with a migration-deficient phenotype. F both, dysmorphic neurons and balloon cells were labelled with antibodies directed against the pS6 Ser236 epitope